Surface-reacted calcium carbonate for desensitizing teeth

ABSTRACT

The present invention relates to surface-reacted calcium carbonate, wherein the surface-reacted calcium carbonate is a reaction product of natural or synthetic calcium carbonate with carbon dioxide and at least one acid. Said calcium carbonate 5 and oral compositions containing the same can be used as a medicament, and especially in treating dentine hypersensitivity.

The present invention relates to new desensitizing agents forhypersensitive teeth and oral care compositions including such agentsand their use.

Dentine is calcified tissue of the body, and along with enamel,cementum, and pulp is one of the four major components of teeth. It isusually covered by enamel on the crown and cementum on the root andsurrounds the entire pulp. Dentine consists of microscopic channels,called dentinal tubules, which radiate outward through the dentine fromthe pulp to the exterior cementum or enamel border.

Dentine hypersensitivity is a common clinical condition usuallyassociated with exposed dentine surfaces. Many diseases, includingphysiological wear, and enamel hypoplasia, wedge shaped defects, andgingival recession, can lead to exposed dentine. It can affect patientsof any age group and most commonly affects the canines and premolars ofboth the arches. Dentine hypersensitivity is characterised by typicalshort sharp pain on the exposed dentine which is aroused by thermal,evaporative, tactile, osmotic or chemical stimuli.

Currently, the most widely accepted mechanism of dentinehypersensitivity is the hydrodynamic theory advanced by Brännström inthe 1960s. According to said theory, dentine hypersensitivity occurswhen the external stimulus such as temperature or a physical or osmoticpressure change contacts exposed dentine and triggers a change in theflow of dentinal fluid. The resultant pressure change across the dentineactivates internal nerve fibres to cause immediate pain. Therefore, oneapproach to treat dentine hypersensitivity is based on the occlusion ofdentinal tubules with materials, reducing dentine permeability, andreducing or preventing dentine fluid flow due to external stimuli.

Oral compositions for treating hypersensitive teeth comprising bioactiveglass and one or more bioadhesive active components are disclosed in WO2010/115041. EP 2 578 272 A1 is concerned with a formulation for oralteeth, comprising a plurality of calcium ion carriers, and a pluralityof calcium-containing particulates, wherein the calcium-containingparticulates are carried by the calcium ion carriers. The effects ofdentifrice containing hydroxyapatite on dentinal tubule occlusion isstudied in Yuan et al., PLOS ONE 2012, 7(12), 1-8. However, all of theseocclusion agents may lead to a complete blocking of the dentinaltubules, which would cut of the flow of nutrients which are supplieddaily to each tubule by the artery that accompanies the nerve and veinin the root canal and keeps the teeth alive and healthy.

In view of the foregoing, there is a continuous need for agents that areuseful in the treatment of dentine hypersensitivity.

Accordingly, it is an object of the present invention to provide adesensitizing agent that can be used in the treatment of dentinehypersensitivity. In particular, it is desirable to provide adesensitizing agent that is easy to apply, can provide instant reliefand is consistently effective. It is also desirable to provide adesensitizing agent that is non-toxic, non-irritant to the pulp, andpainless on application.

It is also an object of the present invention to provide a desensitizingagent that can migrate into the dentine tubules easily and remains inthe tubules and occludes the tubules effectively for a long period afterapplication. It is also desirable to provide a desensitizing agent thatallows a diffuse flow of nutrients into the dentine tubules withoutallowing hydrodynamic flow, which can cause pain. Furthermore, it isdesirable to provide a desensitizing agent that is more resistant toacid challenge.

The foregoing and other objects are solved by the subject-matter asdefined herein in the independent claims.

According to one aspect of the present invention, a surface-reactedcalcium carbonate for use as a medicament is provided, wherein thesurface-reacted calcium carbonate is a reaction product of natural orsynthetic calcium carbonate with carbon dioxide and at least one acid.

According to another aspect of the present invention, surface-reactedcalcium carbonate for use in treating dentine hypersensitivity isprovided, wherein the surface-reacted calcium carbonate is a reactionproduct of natural or synthetic calcium carbonate with carbon dioxideand at least one acid.

According to still another aspect of the present invention, an oral carecomposition for use as a medicament is provided, comprising asurface-reacted calcium carbonate, wherein the surface-reacted calciumcarbonate is a reaction product of natural or synthetic calciumcarbonate with carbon dioxide and at least one acid.

According to still another aspect of the present invention, an oral carecomposition for use in treating dentine hypersensitivity is providedcomprising a surface-reacted calcium carbonate, wherein thesurface-reacted calcium carbonate is a reaction product of natural orsynthetic calcium carbonate with carbon dioxide and at least one acid.

According to still another aspect of the present invention, an oral carecomposition comprising a surface-reacted calcium carbonate is provided,wherein the surface-reacted calcium carbonate is a reaction product ofnatural or synthetic calcium carbonate with carbon dioxide and at leastone acid, and wherein the surface-reacted calcium carbonate is in formof particles having a volume determined top cut particle size (d₉₈) ofequal to or less than 6 μm.

Advantageous embodiments of the present invention are defined in thecorresponding sub-claims.

According to one embodiment the at least one acid is selected from thegroup consisting of hydrochloric acid, sulphuric acid, sulphurous acid,phosphoric acid, citric acid, oxalic acid, acetic acid, formic acid, andmixtures thereof, preferably the at least one acid is selected from thegroup consisting of hydrochloric acid, sulphuric acid, sulphurous acid,phosphoric acid, oxalic acid, and mixtures thereof, and more preferablythe at least one acid is phosphoric acid.

According to one embodiment the surface-reacted calcium carbonate is infort of particles having a volume median grain diameter (d₅₀) of equalto or less than 3 μm, preferably from 1.5 to 2.9 μm, more preferablyfrom 1.7 to 2.7 μm, and most preferably from 2.2 to 2.6 μm, and/or avolume determined top cut particle size (d₉₈) of equal to or less than 6μm, preferably from 3.5 to 5.5 μm, and more preferably from 4.5 to 5 μm.According to another embodiment the surface-reacted calcium carbonate isin form of particles having a specific surface area of from 5 m²/g to200 m²/g, more preferably 20 m²/g to 80 m²/g, and even more preferably30 m²/g to 60 m²/g, measured using nitrogen and the BET method accordingto ISO 9277.

According to one embodiment at least one active agent is associated withthe surface-reacted calcium carbonate, preferably the active agent is atleast one additional desensitizing agent, and more preferably the atleast one additional desensitizing agent is selected from the groupconsisting of potassium nitrate, gluteraldehyde, silver nitrate, zincchloride, strontium chloride hexahydrate, sodium fluoride, stannousfluoride, strontium chloride, strontium acetate, arginine,hydroxyapatite, calcium sodium phosphosilicate, potassium oxalate,calcium phosphate, calcium carbonate, bioactive glasses, and mixturesthereof.

According to one embodiment the surface-reacted calcium carbonate isobtained by a process comprising the steps of:

-   -   a) providing a suspension of natural or synthetic calcium        carbonate,    -   b) adding at least one acid having a pK_(a) value of 0 or less        at 20° C. or having a pK_(a) value from 0 to 2.5 at 20° C. to        the suspension of step a), and

c) treating the suspension of step a) with carbon dioxide before, duringor after step b).

According to another embodiment the surface-reacted calcium carbonate isobtained by a process comprising the steps of:

-   -   A) providing a natural or synthetic calcium carbonate,    -   B) providing at least one water-soluble acid,    -   C) providing gaseous CO₂,    -   D) contacting said natural or synthetic calcium carbonate of        step A) with the at least one acid of step B) and with the CO₂        of step C),    -   characterised in that:    -   i) the at least one acid of step B) has a pK_(a) of greater than        2.5 and less than or equal to 7 at 20° C., associated with the        ionisation of its first available hydrogen, and a corresponding        anion is formed on loss of this first available hydrogen capable        of forming a water-soluble calcium salt, and    -   ii) following contacting the at least one acid with natural or        synthetic calcium carbonate, at least one water-soluble salt,        which in the case of a hydrogen-containing salt has a pK_(a) of        greater than 7 at 20° C., associated with the ionisation of the        first available hydrogen, and the salt anion of which is capable        of forming water-insoluble calcium salts, is additionally        provided.

According to one embodiment the oral care composition comprises from 1to 20 wt.-%, preferably from 1.5 to 15 wt.-%, more preferably from 2 to10 wt.-% of the surface-reacted calcium carbonate, based on the totalweight of the composition. According to another embodiment the oral carecomposition is a toothpaste, a toothpowder, or a mouthwash, and whereinpreferably the surface-reacted calcium carbonate is a reaction productof natural or synthetic calcium carbonate with carbon dioxide andphosphoric acid.

According to one embodiment the oral care composition comprises at leastone additional desensitising agent, preferably selected from the groupconsisting of potassium nitrate, gluteraldehyde, silver nitrate, zincchloride, strontium chloride hexahydrate, sodium fluoride, stannousfluoride, strontium chloride, strontium acetate, arginine,hydroxyapatite, calcium sodium phosphosilicate, potassium oxalate,calcium phosphate, calcium carbonate, bioactive glasses, and mixturesthereof. According to another embodiment the oral care compositioncomprises a bioadhesive polymer, preferably selected from the groupconsisting of hydroxyethyl methacrylate, PEG/PPG copolymers,polyvinylmethylether/maleic anhydride copolymers, polyvinylpyrrolidone(PVP), cross-linked PVP, shellac, polyethylene oxide, methacrylates,acrylates copolymers, methacrylic copolymers, vinylpyrrolidone/vinylacetate copolymers, polyvinyl caprolactum, polylactides, siliconeresins, silicone adhesives, chitosan, milk proteins (casein),amelogenin, ester gum, and combinations thereof.

According to one embodiment the surface-reacted calcium carbonate has aradioactive dentine abrasion (RDA) value of less than 70, preferablyless than 50, and more preferably less than 35. According to anotherembodiment the oral care composition has a pH between 7.5 and 10,preferably between 8 and 9.

It should be understood that for the purpose of the present invention,the following terms have the following meaning.

For the purpose of the present invention, an “acid” is defined asBrønsted-Lowry acid, that is to say, it is an H₃O⁺ ion provider. An“acid salt” is defined as an H₃O⁺ ion-provider, e.g., ahydrogen-containing salt, which is partially neutralised by anelectropositive element. A “salt” is defined as an electrically neutralionic compound formed from anions and cations. A “partially crystallinesalt” is defined as a salt that, on XRD analysis, presents anessentially discrete diffraction pattern.

In accordance with the present invention, pK_(a), is the symbolrepresenting the acid dissociation constant associated with a givenionisable hydrogen in a given acid, and is indicative of the naturaldegree of dissociation of this hydrogen from this acid at equilibrium inwater at a given temperature. Such pK_(a) values may be found inreference textbooks such as Harris, D. C. “Quantitative ChemicalAnalysis: 3^(rd) Edition”, 1991, W.H. Freeman & Co. (USA), ISBN0-7167-2170-8.

In the meaning of the present invention, the “radioactive dentineabrasion (RDA)” is a measure of the erosive effect of abrasives intoothpaste on tooth dentine. It involves using standardised abrasivescompared against the test sample. The determination of this value isdone by determining the activity while cleaning worn dentine which isradioactively marked by mild neutron irradiation. The values obtaineddepend on the size, quantity and surface structure of abrasive used intoothpastes. The RDA value is set by the standards DIN EN ISO 11609.

“Ground calcium carbonate” (GCC) in the meaning of the present inventionis a calcium carbonate obtained from natural sources, such as limestone,marble, dolomite, or chalk, and processed through a wet and/or drytreatment such as grinding, screening and/or fractionating, for example,by a cyclone or classifier.

“Precipitated calcium carbonate” (PCC) in the meaning of the presentinvention is a synthesised material, obtained by precipitation followingreaction of carbon dioxide and lime in an aqueous, semi-dry or humidenvironment or by precipitation of a calcium and carbonate ion source inwater. PCC may be in the vateritic, calcitic or aragonitic crystal form.

For the purpose of the present invention, a “surface-reacted calciumcarbonate” is a material comprising calcium carbonate and an insoluble,at least partially crystalline, non-carbonate calcium salt, preferably,extending from the surface of at least part of the calcium carbonate.The calcium ions forming said at least partially crystallinenon-carbonate calcium salt originate largely from the starting calciumcarbonate material that also serves to form the surface-reacted calciumcarbonate core. Such salts may include OFF anions and/or crystal water.

In the meaning of the present invention “water-insoluble” materials aredefined as materials which, when mixed with deionised water and filteredon a filter having a 0.2 μm pore size at 20° C. to recover the liquidfiltrate, provide less than or equal to 0.1 g of recovered solidmaterial following evaporation at 95 to 100° C. of 100 g of said liquidfiltrate. “Water-soluble” materials are defined as materials leading tothe recovery of greater than 0.1 g of recovered solid material followingevaporation at 95 to 100° C. of 100 g of said liquid filtrate.

Throughout the present document, the “particle size” of a calciumcarbonate and other materials is described by its distribution ofparticle sizes. The value represents the diameter relative to which x %by weight of the particles have diameters less than d_(x). This meansthat the d₂₀ value is the particle size at which 20 wt.-% of allparticles are smaller, and the d₇₅ value is the particle size at which75 wt.-% of all particles are smaller. The d₅₀ value is thus the weightmedian particle size, i.e. 50 wt.-% of all grains are bigger or smallerthan this particle size. For the purpose of the present invention theparticle size is specified as weight median particle size d₅₀ unlessindicated otherwise. For determining the weight median particle size d₅₀value a Sedigraph can be used. For the purpose of the present invention,the “particle size” of surface-reacted calcium is described, as volumedetermined particle size distributions. For determining the volumedetermined particle size distribution, e.g., the volume median graindiameter (d₅₀) or the volume determined top cut particle size (d₉₈) ofsurface-reacted calcium carbonate, a Malvern Mastersizer 2000 can beused. The weight determined particle size distribution may correspond tothe volume determined particle size if the density of all the particlesis equal.

A “specific surface area (SSA)” of a calcium carbonate in the meaning ofthe present invention is defined as the surface area of the calciumcarbonate divided by its mass. As used herein, the specific surface areais measured by nitrogen gas adsorption using the BET isotherm (ISO9277:2010) and is specified in m²/g.

An “oral care composition” in the meaning of the present inventionrefers to a composition suitable for the use in the mouth and forveterinary and/or human applications but especially for use inapplications for the human mouth.

For the purpose of the present invention, the term “viscosity” or“Brookfield viscosity” refers to Brookfield viscosity. The Brookfieldviscosity is for this purpose measured by a Brookfield (Typ RVT)viscometer at 20° C.±2° C. at 100 rpm using an appropriate spindle andis specified in mPa·s.

A “suspension” or “slurry” in the meaning of the present inventioncomprises insoluble solids and water, and optionally further additives,and usually contains large amounts of solids and, thus, is more viscousand can be of higher density than the liquid from which it is formed.

Where the term “comprising” is used in the present description andclaims, it does not exclude other elements. For the purposes of thepresent invention, the term “consisting of” is considered to be apreferred embodiment of the term “comprising of”. If hereinafter a groupis defined to comprise at least a certain number of embodiments, this isalso to be understood to disclose a group, which preferably consistsonly of these embodiments.

Where an indefinite or definite article is used when referring to asingular noun, e.g. “a”, “an” or “the”, this includes a plural of thatnoun unless something else is specifically stated.

Terms like “obtainable” or “definable” and “obtained” or “defined” areused interchangeably. This e.g. means that, unless the context clearlydictates otherwise, the term “obtained” does not mean to indicate thate.g. an embodiment must be obtained by e.g. the sequence of stepsfollowing the term “obtained” though such a limited understanding isalways included by the terms “obtained” or “defined” as a preferredembodiment.

According to the present invention, a surface-reacted calcium carbonateis used as a medicament. The surface-reacted calcium carbonate is areaction product of natural or synthetic calcium carbonate with carbondioxide and at least one acid.

In the following the details and preferred embodiments of the inventivesurface-reacted calcium carbonate will be set out in more details. It isto be understood that these technical details and embodiments also applyto the inventive method for producing the surface-reacted calciumcarbonate as well as to the inventive compositions comprising thesurface-reacted calcium carbonate.

The Surface-Reacted Calcium Carbonate

According to the present invention, the surface-reacted calciumcarbonate is a reaction product of natural or synthetic calciumcarbonate with carbon dioxide and at least one acid.

Natural (or ground) calcium carbonate (GCC) is understood to be anaturally occurring form of calcium carbonate, mined from sedimentaryrocks such as limestone or chalk, or from metamorphic marble rocks.Calcium carbonate is known to exist mainly as three types of crystalpolymorphs: calcite, aragonite and vaterite. Calcite, the most commoncrystal polymorph, is considered to be the most stable crystal form ofcalcium carbonate. Less common is aragonite, which has a discrete orclustered needle orthorhombic crystal structure. Vaterite is the rarestcalcium carbonate polymorph and is generally unstable. Natural calciumcarbonate is almost exclusively of the calcitic polymorph, which is saidto be trigonal-rhombohedral and represents the most stable of thecalcium carbonate polymorphs. The term “source” of the calcium carbonatein the meaning of the present invention refers to the naturallyoccurring mineral material from which the calcium carbonate is obtained.The source of the calcium carbonate may comprise further naturallyoccurring components such as magnesium carbonate, alumino silicate etc.

According to one embodiment of the present invention, the naturalcalcium carbonate is selected from the group consisting of marble,chalk, dolomite, limestone and mixtures thereof.

According to one embodiment of the present invention the GCC is obtainedby dry grinding. According to another embodiment of the presentinvention the GCC is obtained by wet grinding and optionally subsequentdrying.

In general, the grinding step can be carried out with any conventionalgrinding device, for example, under conditions such that comminutionpredominantly results from impacts with a secondary body, i.e. in one ormore of: a ball mill, a rod mill, a vibrating mill, a roll crusher, acentrifugal impact mill, a vertical bead mill, an attrition mill, a pinmill, a hammer mill, a pulveriser, a shredder, a de-dumper, a knifecutter, or other such equipment known to the skilled man. In case thecalcium carbonate containing mineral material comprises a wet groundcalcium carbonate containing mineral material, the grinding step may beperformed under conditions such that autogenous grinding takes placeand/or by horizontal ball milling, and/or other such processes known tothe skilled man. The wet processed ground calcium carbonate containingmineral material thus obtained may be washed and dewatered by well-knownprocesses, e.g. by flocculation, filtration or forced evaporation priorto drying. The subsequent step of drying may be carried out in a singlestep such as spray drying, or in at least two steps. It is also commonthat such a mineral material undergoes a beneficiation step (such as aflotation, bleaching or magnetic separation step) to remove impurities.

“Precipitated calcium carbonate” (FCC) in the meaning of the presentinvention is a synthesized material, generally obtained by precipitationfollowing reaction of carbon dioxide and lime in an aqueous environmentor by precipitation of a calcium and carbonate ion source in water or byprecipitation of calcium and carbonate ions, for example CaCl₂ andNa₂CO₃, out of solution. Further possible ways of producing PCC are thelime soda process, or the Solvay process in which PCC is a by-product ofammonia production. Precipitated calcium carbonate exists in threeprimary crystalline forms: calcite, aragonite and vaterite, and thereare many different polymorphs (crystal habits) for each of thesecrystalline forms. Calcite has a trigonal structure with typical crystalhabits such as scalenohedral (S-PCC), rhombohedral (R-PCC), hexagonalprismatic, pinacoidal, colloidal (C-PCC), cubic, and prismatic (P-PCC).Aragonite is an orthorhombic structure with typical crystal habits oftwinned hexagonal prismatic crystals, as well as a diverse assortment ofthin elongated prismatic, curved bladed, steep pyramidal, chisel shapedcrystals, branching tree, and coral or worm-like form. Vaterite belongsto the hexagonal crystal system. The obtained PCC slurry can bemechanically dewatered and dried.

According to one embodiment of the present invention, the syntheticcalcium carbonate is precipitated calcium carbonate, preferablycomprising aragonitic, vateritic or calcitic mineralogical crystal formsor mixtures thereof.

According to one embodiment of the present invention, the natural orsynthetic calcium carbonate is ground prior to the treatment with carbondioxide and at least one acid. The grinding step can be carried out withany conventional grinding device such as a grinding mill known to theskilled person.

According to one embodiment of the present invention, the natural orsynthetic calcium carbonate is in form of particles having a weightmedian particle size d₅₀ of equal to or less than 3 μm, preferably from1.5 to 2.9 μm, more preferably from 1.7 to 2.7 μm, and most preferablyfrom 2.2 to 2.6 μm. According to a further embodiment of the presentinvention, the natural or synthetic calcium carbonate is in form ofparticles having a top cut particle size d₉₈ of equal to or less than 6μm, preferably from 3.5 to 5.5 μm, and more preferably from 4.5 to 5.0μm.

Preferably the surface-reacted calcium carbonate to be used in thepresent invention is prepared as an aqueous suspension having a pH,measured at 20° C., of greater than 6.0, preferably greater than 6.5,more preferably greater than 7.0, even more preferably greater than 7.5.

In a preferred process for the preparation of the aqueous suspension ofsurface-reacted calcium carbonate, the natural or synthetic calciumcarbonate, either finely divided, such as by grinding, or not, issuspended in water. Preferably, the slurry has a content of natural orsynthetic calcium carbonate within the range of 1 wt.-% to 90 wt.-%,more preferably 3 wt.-% to 60 wt.-%, and even more preferably 5 wt.-% to40 wt.-%, based on the weight of the slurry.

In a next step, at least one acid is added to the aqueous suspensioncontaining the natural or synthetic calcium carbonate. The at least oneacid can be any strong acid, medium-strong acid, or weak acid, ormixtures thereof, generating H₃O⁺ ions under the preparation conditions.According to the present invention, the at least one acid can also be anacidic salt, generating H₃O⁺ ions under the preparation conditions.

According to one embodiment, the at least one acid is a strong acidhaving a pK_(a) of 0 or less at 20° C. According to another embodiment,the at least one acid is a medium-strong acid having a pK_(a) value from0 to 2.5 at 20° C. If the pK_(a) at 20° C. is 0 or less, the acid ispreferably selected from sulphuric acid, hydrochloric acid, or mixturesthereof. If the pK_(a) at 20° C. is from 0 to 2.5, the acid ispreferably selected from H₂SO₃, H₃PO₄, oxalic acid, or mixtures thereof.The at least one acid can also be an acidic salt, for example, HSO₄ ⁻ orH₂PO₄ ⁻, being at least partially neutralized by a corresponding cationsuch as Li⁺, Na⁺ or K⁺, or HPO₄ ²⁻, being at least partially neutralisedby a corresponding cation such as Li⁺, Na⁺ Mg²⁺ or Ca²⁺. The at leastone acid can also be a mixture of one or more acids and one or moreacidic salts.

According to still another embodiment, the at least one acid is a weakacid having a pK_(a) value of greater than 2.5 and less than or equal to7, when measured at 20° C., associated with the ionisation of the firstavailable hydrogen, and having a corresponding anion formed on loss ofthis first available hydrogen, which is capable of forming water-solublecalcium salts. According to the preferred embodiment, the weak acid hasa pK_(a) value from 2.6 to 5 at 20° C., and more preferably the weakacid is selected from the group consisting of acetic acid, formic acid,propanoic acid, and mixtures thereof.

In case a weak acid is used, after addition of said acid to the aqueoussuspension containing the natural or synthetic calcium carbonate, atleast one water-soluble salt, which in the case of a hydrogen-containingsalt has a pK_(a) of greater than 7, when measured at 20° C., associatedwith the ionisation of the first available hydrogen, and the salt anionof which is capable of forming water-insoluble calcium salts, isadditionally added. The cation of said water-soluble salt is preferablyselected from the group consisting of potassium, sodium, lithium andmixtures thereof. In a more preferred embodiment, said cation is sodium.It is of note that depending on the charge of the anion, more than oneof said cations may be present to provide an electrically neutral ioniccompound. The anion of said water-soluble salt is preferably selectedfrom the group consisting of phosphate, dihydrogen phosphate,monohydrogen phosphate, oxalate, silicate, mixtures thereof and hydratesthereof. In a more preferred embodiment, said anion is selected from thegroup consisting of phosphate, dihydrogen phosphate, monohydrogenphosphate, mixtures thereof and hydrates thereof. In a most preferredembodiment, said anion is selected from the group consisting ofdihydrogen phosphate, monohydrogen phosphate, mixtures thereof andhydrates thereof. Water-soluble salt addition may be performed dropwiseor in one step. In the case of drop wise addition, this additionpreferably takes place within a time period of 10 minutes. It is morepreferred to add said salt in one step.

According to one embodiment of the present invention, the at least oneacid is selected from the group consisting of hydrochloric acid,sulphuric acid, sulphurous acid, phosphoric acid, citric acid, oxalicacid, acetic acid, formic acid, and mixtures thereof. Preferably the atleast one acid is selected from the group consisting of hydrochloricacid, sulphuric acid, sulphurous acid, phosphoric acid, oxalic acid,H₂PO₄ ⁻, being at least partially neutralised by a corresponding cationsuch as Li⁺, Na⁺ or K⁺HPO₄ ²⁻, being at least partially neutralised by acorresponding cation such as Li⁺, Na⁺ Mg²⁺, or Ca²⁺, and mixturesthereof, more preferably the at least one acid is selected from thegroup consisting of hydrochloric acid, sulphuric acid, sulphurous acid,phosphoric acid, oxalic acid, or mixtures thereof, and most preferably,the at least one acid is phosphoric acid. Without being bound to anytheory, the inventors believe that the use of phosphoric acid can bebeneficial in therapy, especially in treating dentine hypersensitivity.

The at least one acid can be added to the suspension as a concentratedsolution or a more diluted solution. Preferably, the molar ratio of theat least one acid to the natural or synthetic calcium carbonate is from0.05 to 4, more preferably from 0.1 to 2.

As an alternative, it is also possible to add the at least one acid tothe water before the natural or synthetic calcium carbonate issuspended.

According to the present invention, the surface-reacted calciumcarbonate is obtained by treating the natural or synthetic calciumcarbonate with carbon dioxide. The carbon dioxide can be formed in situby the acid treatment and/or can be supplied from an external source. Ifa strong acid such as sulphuric acid or hydrochloric acid ormedium-strong acid such as phosphoric acid is used for the acidtreatment of the natural or synthetic calcium carbonate, the carbondioxide is automatically formed. Alternatively or additionally, thecarbon dioxide can be supplied from an external source.

According to one embodiment, the surface-reacted calcium carbonate is areaction product of natural or synthetic calcium carbonate with carbondioxide and at least one acid, wherein the carbon dioxide is formed insitu as a result of contacting the at least one acid with the natural orsynthetic calcium carbonate and/or is supplied from an external source.

Acid treatment and treatment with carbon dioxide can be carried outsimultaneously which is the case when a strong or medium-strong acid isused. It is also possible to carry out acid treatment first, e.g. with amedium strong acid having a pK_(a) in the range of 0 to 2.5 at 20° C.,wherein carbon dioxide is formed in situ, and thus, the carbon dioxidetreatment will automatically be carried out simultaneously with the acidtreatment, followed by the additional treatment with carbon dioxidesupplied from an external source.

Preferably, the concentration of gaseous carbon dioxide in thesuspension is, in terms of volume, such that the ratio (volume ofsuspension):(volume of gaseous CO₂) is from 1:0.05 to 1:20, even morepreferably from 1:0.05 to 1:5.

In a preferred embodiment, the acid treatment step and/or the carbondioxide treatment step are repeated at least once, more preferablyseveral times. According to one embodiment, the at least one acid isadded over a time period of at least 30 min, preferably at least 45 min,and more preferably at least 1 h.

Subsequent to the acid treatment arid carbon dioxide treatment, the pHof the aqueous suspension, measured at 20° C., naturally reaches a valueof greater than 6.0, preferably greater than 6.5, more preferablygreater than 7.0, even more preferably greater than 7.5, therebypreparing the surface-reacted calcium carbonate as an aqueous suspensionhaving a pH of greater than 6.0, preferably greater than 6.5, morepreferably greater than 7.0, even more preferably greater than 7.5. Ifthe aqueous suspension is allowed to reach equilibrium, the pH isgreater than 7. A pH of greater than 6.0 can be adjusted without theaddition of a base when stirring of the aqueous suspension is continuedfor a sufficient time period, preferably 1 hour to 10 hours, morepreferably 1 to 5 hours.

Alternatively, prior to reaching equilibrium, which occurs at a pHgreater than 7, the pH of the aqueous suspension may be increased to avalue greater than 6 by adding a base subsequent to carbon dioxidetreatment. Any conventional base such as sodium hydroxide or potassiumhydroxide can be used.

Further details about the preparation of the surface-reacted naturalcalcium carbonate are disclosed in WO 00/39222 and US 2004/0020410,wherein the surface-reacted natural calcium carbonate is described as afiller for paper manufacture. The preparation of surface-reacted calciumcarbonate with weak acids is disclosed in EP 2 264 108. The preparationof surface-reacted calcium carbonate and its use in purificationprocesses is disclosed in EP 1 974 806, EP 1 982 759, and EP 1 974 807.The use of surface-reacted calcium carbonate as carrier for thecontrolled release of active agents is described in WO 2010/037753.

Similarly, surface-reacted precipitated calcium carbonate is obtained.As can be taken in detail from EP 2 070 991, surface-reactedprecipitated calcium carbonate is obtained by contacting precipitatedcalcium carbonate with H₃O⁺ ions and with anions being solubilised in anaqueous medium and being capable of forming water-insoluble calciumsalts, in an aqueous medium to form a slurry of surface-reactedprecipitated calcium carbonate, wherein said surface-reactedprecipitated calcium carbonate comprises an insoluble, at leastpartially crystalline calcium salt of said anion formed on the surfaceof at least part of the precipitated calcium carbonate.

Said solubilised calcium ions correspond to an excess of solubilisedcalcium ions relative to the solubilised calcium ions naturallygenerated on dissolution of precipitated calcium carbonate by H₃O⁺ ions,where said H₃O⁺ ions are provided solely in the form of a counterion tothe anion, i.e. via the addition of the anion in the form of an acid ornon-calcium acid salt, and in absence of any further calcium ion orcalcium ion generating source.

Said excess solubilised calcium ions are preferably provided by theaddition of a soluble neutral or acid calcium salt, or by the additionof an acid or a neutral or acid non-calcium salt which generates asoluble neutral or acid calcium salt in situ.

Said H₃O⁺ ions may be provided by the addition of an acid or an acidsalt of said anion, or the addition of an acid or an acid salt whichsimultaneously serves to provide all or part of said excess solubilisedcalcium ions.

According to one embodiment of the present invention, thesurface--reacted calcium carbonate is obtained by a process comprisingthe steps of:

-   -   a) providing a suspension of natural or synthetic calcium        carbonate,    -   b) adding at least one acid having a pK_(a) value of 0 or less        at 20° C. or having a pK_(a) value from 0 to 2.5 at 20° C. to        the suspension of step a), and    -   c) treating the suspension of step a) with carbon dioxide        before, during or after step b).

According to one embodiment, at least one acid having a pK_(a) value of0 or less at 20° C. is added in step b) to the suspension of step a).According to another embodiment, at least one acid having a pK_(a) valuefrom 0 to 2.5 at 20° C. is added in step b) to the suspension of stepa).

The carbon dioxide used in step c) can be formed in situ by the acidtreatment of step b) and/or can be supplied from an external source.

According to one embodiment of the present invention, thesurface-reacted calcium carbonate is obtained by a process comprisingthe steps of:

-   -   A) providing a natural or synthetic calcium carbonate,    -   B) providing at least one water-soluble acid,    -   C) providing gaseous CO₂,    -   D) contacting said natural or synthetic calcium carbonate of        step A) with the at least one acid of step B) and with the CO₂        of step C),    -   characterised in that:    -   i) the at least one acid of step B) has a pK_(a) of greater than        2.5 and less than or equal to 7 at 20° C., associated with the        ionisation of its first available hydrogen, and a corresponding        anion is formed on loss of this first available hydrogen capable        of forming a water-soluble calcium salt, and    -   ii) following contacting the at least one acid with natural or        synthetic calcium carbonate, at least one water-soluble salt,        which in the case of a hydrogen-containing salt has a pK_(a) of        greater than 7 at 20° C., associated with the ionisation of the        first available hydrogen, and the salt anion of which is capable        of forming water-insoluble calcium salts, is additionally        provided.

The surface-reacted calcium carbonate can be, kept in suspension,optionally further stabilised by a dispersant. Conventional dispersantsknown to the skilled person can be used. A preferred dispersant ispolyacrylic acid.

Alternatively, the aqueous suspension described above can be dried,thereby obtaining the solid (i.e. dry or containing as little water thatit is not in a fluid form) surface-reacted natural or synthetic calciumcarbonate in the form of granules or a powder.

According to one embodiment of the present invention, thesurface-reacted calcium carbonate has a specific surface area of from 5m²/g to 200 m²/g, more preferably 20 m²/g to 80 m²/g and even morepreferably 30 m²/g to 60 m²/g, measured using nitrogen and the BETmethod according to ISO 9277.

The particle size of the surface-reacted calcium carbonate can betailored with respect to the dentine tubules to be treated. For example,in case of a human molar, wherein the dentine tubules typically have adiameter between 3 and 2 μm, the surface-reacted calcium carbonateparticles may have a volume median grain diameter (d₅₀) of equal to orless than 3 μm.

According to one embodiment of the present invention, thesurface-reacted calcium carbonate is in form of particles having avolume median grain diameter (d₅₀) of equal to or less than 3 μm,preferably from 1.5 to 2.9 μm, more preferably from 1.7 to 2.7 μm, andmost preferably from 2.2 to 2.6 μm. According to another embodiment ofthe present invention, the surface-reacted calcium carbonate is in formof particles having a volume determined top cut particle size (d₉₈) ofequal to or less than 6 μm, preferably from 3.5 to 5.5 μm, and morepreferably from 4.5 to 5 μm. According to a preferred embodiment of thepresent invention, the surface-reacted calcium carbonate is in form ofparticles having volume median grain diameter (d₅₀) of equal to or lessthan 3 μm, preferably from 1.5 to 2.9 μm, more preferably from 1.7 to2.7 μm, and most preferably from 2.2 to 2.6 μm, and having a volumedetermined top cut particle size (d₉₈) of equal to or less than 6 μm,preferably from 3.5 to 5.5 μm, and more preferably from 4.5 to 5 μm. Thevolume median grain diameter (d₅₀) and volume determined top cutparticle size (d₉₈) can be determined by laser diffraction measurements,for example, by using a Malvern Mastersizer 2000.

According to one embodiment of the present invention, thesurface-reacted calcium carbonate comprises an insoluble, at leastpartially crystalline calcium salt of an anion of the at least one acid,which is formed on the surface of the natural or synthetic calciumcarbonate. According to one embodiment, the insoluble, at leastpartially crystalline salt of an anion of the at least one acid coversthe surface of the natural or synthetic calcium carbonate at leastpartially, preferably completely. Depending on the employed at least oneacid, the anion may be sulphate, sulphite, phosphate, citrate, oxalate,acetate, formiate and/or chloride.

According to one preferred embodiment, the surface-reacted calciumcarbonate is a reaction product of natural calcium carbonate and atleast one acid, preferably phosphoric acid.

The surface-reacted calcium carbonate is also capable of associating andtransporting an active agent. The association preferably is anadsorption onto the surface of the surface-reacted calcium carbonateparticles, be it the outer or the inner surface of the particles or anabsorption into the particles, which is possible due to their porosity.In this respect, it is believed that because of the intra and interporestructure of the surface reacted calcium carbonate, this material is asuperior agent to deliver previously ad/absorbed materials over timerelative to common materials having similar specific surface areas.

The surface-reacted calcium carbonate may have an intra particleporosity within the range from 5 vol.-% to 50 vol.-%, preferably from 20vol.-% to 50 vol.-%, and more preferably from 30 vol.-% to 50 vol.-%,calculated from mercury porosimetry measurement. From the bimodalderivative pore size distribution curve the lowest point between thepeaks indicates the diameter where the intra and inter-particle porevolumes can be separated. The pore volume at diameters greater than thisdiameter is the pore volume associated with the inter-particle pores.The total pore volume minus this inter particle pore volume gives theintra particle pore volume from which the intra particle porosity can becalculated, preferably as a fraction of the solid material volume, asdescribed in Transport in Porous Media (2006) 63: 239-259. Furtherdetails with respect to the porosity of the surface-reacted calciumcarbonate and its use as agent for delivering materials can be found inWO 2010/037753.

Thus, generally, any agent fitting into the intra- and/or inter particlepores of the surface-reacted calcium carbonate carrier is suitable to betransported by the surface-reacted calcium carbonate carriers accordingto the invention. For example, active agents such as those selected fromthe group comprising pharmaceutically active agents, biologically activeagents, disinfecting agents, preservatives such as triclosan, flavouringagents, surfactants like defoamers, or additional desensitizing agentscan be used. According to one embodiment, at least one active agent isassociated with the surface-reacted calcium carbonate. According to apreferred embodiment the active agent is at least one additionaldesensitizing agent, preferably selected from the group consisting ofpotassium nitrate, gluteraldebyde, silver nitrate, zinc chloride,strontium chloride hexahydrate, sodium fluoride, stannous fluoride,strontium chloride, strontium acetate, arginine, hydroxyapatite, calciumsodium phosphosilicate, potassium oxalate, calcium phosphate, calciumcarbonate, bioactive glasses, and mixtures thereof.

The Oral Care Composition

The oral care composition for the use according to the present inventioncomprises a surface-reacted calcium carbonate, wherein thesurface-reacted calcium carbonate is a reaction product of natural orsynthetic calcium carbonate with carbon dioxide and at least one acid.

According to one embodiment of the present invention, the compositioncomprises from 1 to 20 wt.-%, preferably from 1.5 to 15 wt.-%, morepreferably from 2 to 10 wt.-% of the surface-reacted calcium carbonate,based on the total weight of the composition.

The surface-reacted calcium carbonate can consist of only one type ofsurface-reacted calcium carbonate or can be a mixture of two or moretypes of surface-reacted calcium carbonate. The oral care composition ofthe present invention may contain the surface-reacted calcium carbonateas the only desensitizing agent. Alternatively, the oral carecomposition of the present invention may contain the surface-reactedcalcium carbonate in combination with at least one additionaldesensitising agent. According to one embodiment, the oral carecomposition comprises at least one additional desensitising agent.Preferably, the additional desensitising agent is selected from thegroup consisting of potassium nitrate, gluteraldehyde, silver nitrate,zinc chloride, strontium chloride hexahydrate, sodium fluoride, stannousfluoride, strontium chloride, strontium acetate, arginine,hydroxyapatite, calcium sodium phosphosilicate, potassium oxalate,calcium phosphate, calcium carbonate, bioactive glasses, and mixturesthereof.

According to one embodiment, the additional desensitizing agent has aweight median particle size d₅₀ from 0.1 to 100 μm, preferably from 0.5to 50 μm, more preferably from 1 to 20 μm, and most preferably from 2 to10 μm.

The at least one additional desensitizing agent can be present in theoral care composition in an amount from 1 to 20 wt.-%, preferably from1.5 to 15 wt.-%, more preferably from 2 to 10 wt.-%, based on the totalweight of the composition.

According to one embodiment, the oral care composition of the presentinvention comprises from 1 to 20 wt.-% of the surface-reacted calciumcarbonate and from 1 to 20 wt.-% of an additional desensitising agent,based on the total weight of the composition.

The oral care composition of the present invention can be, for example,a toothpaste, a toothpowder, a varnish, an adhesive gel, a cement, aresin, a spray, a foam, a balm, a composition carried out on amouthstrip or a buccal adhesive patch, a chewable tablet, a chewablepastille, a chewable gum, a lozenge, a beverage, or a mouthwash.According to one embodiment of the present invention, the oral carecomposition is a toothpaste, a toothpowder, or a mouthwash, andpreferably a toothpaste.

According to a preferred embodiment, the oral care composition is atoothpaste, a toothpowder, or a mouthwash and the surface-reactedcalcium carbonate is a reaction product of natural or synthetic calciumcarbonate with carbon dioxide and phosphoric acid. According to anotherpreferred embodiment, the oral care composition is a toothpaste, atoothpowder, or a mouthwash and the surface-reacted calcium carbonate isa reaction product of natural or synthetic calcium carbonate with carbondioxide and phosphoric acid, wherein the surface-reacted calciumcarbonate is in form of particles having a volume median grain diameter(d₅₀) of equal to or less than 3 μm, preferably from 1.5 to 2.9 μm, morepreferably from 1.7 to 2.7 μm, and most preferably from 2.2 to 2.6 μm,and/or having a volume determined top cut particle size (d₉₈) of equalto or less than 6 μm, preferably from 3.5 to 5.5 μm, and more preferablyfrom 4.5 to 5 μm.

The surface-reacted calcium carbonate can consist of one type ofsurface-reacted calcium carbonate or can be a mixture of two or moretypes of surface-reacted calcium carbonate. According to one embodiment,the surface-reacted calcium carbonate has a radioactive dentine abrasion(RDA) value of less than 70, preferably less than 50, and morepreferably less than 35. According to one embodiment of the presentinvention, the oral care composition is a toothpaste for sensitive teethand/or for children's teeth, and preferably the surface-reacted calciumcarbonate has an RDA of less than 50, and most preferably less than 35.

According to one embodiment of the present invention, the oral carecomposition has a pH between 7.5 and 10, preferably between 8 and 9.

According to one embodiment of the present invention, the oral carecomposition comprises a surface-reacted calcium carbonate, wherein thesurface-reacted calcium carbonate is a reaction product of natural orsynthetic calcium carbonate with carbon dioxide and at least one acid,and wherein the surface-reacted calcium carbonate is in form ofparticles having a volume determined top cut particle size (d₉₈) ofequal to or less than 6 μm.

In addition to the surface-reacted calcium carbonate and the optionaladditional desensitizing agent, the oral care composition may furthercomprise bioadhesive polymers, fluoride compounds, surfactants, binders,humectants, remineralisers, flavouring agents, sweetening agents and/orwater.

According to one embodiment of the present invention, the oral carecomposition comprises a bioadhesive polymer. The bioadhesive polymer mayinclude any polymer that promotes adhesion of the surface-reactedcalcium carbonate to teeth or tooth surface and remains on the teeth ortooth surface for an extended period of time, for example, 1 hour, 3hours, 5 hours, 10 hours, 24 hours. In certain embodiments, thebioadhesive polymer may become more adhesive when the oral carecomposition is moistened with, for example, water or saliva. In otherembodiments, the bioadhesive polymer is a material or combination ofmaterials that enhance the retention of the active ingredient on theteeth or a tooth surface onto which the composition is applied. Suchbioadhesive polymers include, for example, hydrophilic organic polymers,hydrophobic organic polymers, silicone gums, silicas, and combinationsthereof. According to one embodiment, the bioadhesive polymer isselected from the group consisting of hydroxyethyl methacrylate, PEG/PPGcopolymers, polyvinylmethylether/maleic anhydride copolymers,polyvinylpyrrolidone (PVP), cross-linked PVP, shellac, polyethyleneoxide, methacrylates, acrylates copolymers, methacrylic copolymers,vinylpyrrolidone/vinyl acetate copolymers, polyvinyl caprolactum,polylactides, silicone resins, silicone adhesives, chitosan, milkproteins (casein), amelogenin, ester gum, and combinations thereof.

Examples of suitable fluoride compounds sodium fluoride, stannousfluoride, sodium monofluorophosphate, potassium fluoride, potassiumstannous fluoride, sodium fluorostannate, stannous chlorofluoride andamine fluoride. The fluoride compounds may be added in an amount from0.1 to 2 wt.-%, based on the total weight of the oral care composition.Good results can be achieved employing an amount of fluoride compound toprovide available fluoride ion in the range of 300 to 2 000 ppm in theoral care composition, preferably about 1 450 ppm.

Suitable surfactants are generally anionic organic synthetic surfactantsthroughout a wide pH range. Representative of such surfactants used inthe range of about 0.5 to 5 wt.-%, based on the total weight of the oralcare composition, are water-soluble salts of C₁₀-C₁₈ alkyl sulphates,such as sodium lauryl sulphate, of sulphonated monoglycerides of fattyacids, such as sodium monoglyceride sulphonates, of fatty acid amides oftaurine, such as sodium N-methyl-N-palmitoyltauride, and of fatty acidesters of isethionic acid, and aliphatic acylamides, such as sodiumN-lauroyl sarcosinate. However, surfactants obtained from naturalsources such as cocamidopropyl betaine may also be used.

Suitable binders or thickening agents to provide the desired consistencyare, for example, hydroxyethylcellulose, sodium carboxymethylcellulose,natural gums, such as gum karaya, gum arabic, gum tragacanth, xanthangum or cellulose gum, colloidal silicates, or finely divided silica.Generally, from 0.5 to 5 wt.-%, based on the total weight of the oralcare composition, can be used.

Various humectants known to the skilled person can be used, such asglycerine, sorbitol and other polyhydric alcohols, for example, in anamount from 20 to 40 wt.-%, based on the total weight of the oral carecomposition. Examples of suitable flavouring agents include oil ofwintergreen, oil of spearmint, oil of peppermint, oil of clove, oil ofsassafras and the like. Saccharin, aspartame, dextrose, or levulose canbe used as sweetening agents, for example, in an amount from 0.01 to 1wt.-%, based on the total weight of the oral care composition.Preservatives such as sodium benzoate may be present in an amount from0.01 to 1 wt.-%, based on the total weight of the oral care composition.Colorants such as titanium dioxide may also be added to the oral carecomposition, for example, in an amount from 0.01 to 1 wt.-%, based onthe total weight of the oral care composition.

The oral care composition of the present invention also contain amaterial selected from the group consisting of silica, precipitatedsilica, alumina, aluminosilicate, metaphosphate, tricalcium phosphate,calcium pyrophosphate, ground calcium carbonate, precipitated calciumcarbonate, sodium bicarbonate, bentonite, kaolin, aluminium hydroxide,calcium hydrogen phosphate, hydroxylapatite, and mixtures thereof.According to one embodiment, the oral care composition contains amaterial being selected from ground calcium carbonate and/orprecipitated silica. According to another embodiment, the oral carecomposition contains a material being selected from the group consistingof ground calcium carbonate, precipitated calcium carbonate, aluminiumhydroxide, calcium hydrogen phosphate, silica, hydroxylapatite, andmixtures thereof. According to a preferred embodiment of the presentinvention, the oral care composition comprises surface-reacted calciumcarbonate, wherein the surface-reacted calcium carbonate is a reactionproduct of natural or synthetic calcium carbonate with carbon dioxideand at least one acid, and calcium carbonate, preferably ground calciumcarbonate and/or precipitated calcium carbonate.

According to one embodiment of the present invention, the oral carecomposition is a tooth paste. The toothpaste may be produced by a methodcomprising the following steps:

-   -   I) providing a mixture of water and a humectants, and optionally        at least one of a thickener, a preservative, a fluoride, and a        sweetener,    -   II) adding a surface-reacted calcium carbonate, and optionally a        colorant, to the mixture of step I), wherein the surface-reacted        calcium carbonate is a reaction product of natural or synthetic        calcium carbonate with carbon dioxide and at least one acid,    -   III) adding a surfactant to the mixture of step II), and    -   IV) optionally, adding a flavouring agent to the mixture of step        III).

However, a toothpaste of the present invention may also be produced byany other method known to the skilled person.

Therapeutic Use

It was found that surface-reacted calcium carbonate can be used intherapy, and especially in dental therapy. According to the presentinvention, a surface-reacted calcium carbonate for use as a medicamentis provided, wherein the surface-reacted calcium carbonate is a reactionproduct of natural or synthetic calcium carbonate with carbon dioxideand at least one acid. According to a further aspect of the presentinvention, an oral care composition for use as a medicament is provided,comprising a surface-reacted calcium carbonate, wherein thesurface-reacted calcium carbonate is a reaction product of natural orsynthetic calcium carbonate with carbon dioxide and at least one acid.

According to one embodiment, the surface-reacted calcium carbonate ofthe present invention or the oral care composition of the presentinvention is used in treating dentine hypersensitivity.

The inventors of the present invention surprisingly found thatsurface-reacted calcium carbonate is useful in therapy, for example,dental therapy, and especially in the treatment of dentinehypersensitivity. Surface-reacted calcium carbonate differs fromconventional calcium carbonate in several aspects. For example, unlikeconventional calcium carbonate, surface-reacted calcium carbonatecomprises a porous, platy or lamellar surface structure (see FIGS. 1 and2). Without being bound to any theory, it is believed that due to itsporous platy or lamellar surface structure, the surface-reacted calciumcarbonate can occlude the dentine tubules without cutting of the diffuseflow of nutrients into the dentine tubules. It is also believed that dueto its special surface-structure, the surface-modified calcium carbonatecan interlock in the dentine tubules by a mechanism of canting due toits lamellar surface structure, and thus, can remain within the tubulesfor a long time period. Furthermore, the surface treatment renders thesurface-reacted calcium carbonate more resistant against acids.Therefore, the surface-reacted calcium carbonate is more stable underacidic conditions, for example, during consumption of acidic beveragessuch as soft drinks or acidic dishes such as salads with vinegar-baseddressings.

The surface-reacted calcium carbonate of the present invention and/ororal compositions comprising the same may be used in professional,in-office treatment or in at home treatment.

According to one embodiment, the surface-reacted calcium carbonate foruse in treating dentine hypersensitivity is used in a method comprisingadministering to at least one tooth of a patient a therapeuticallyeffective amount of the surface-reacted calcium carbonate at least oncea day, preferably twice a day and more preferably three-times a day. A“therapeutically effective” amount of the surface-reacted calciumcarbonate is an amount that is sufficient to have the desiredtherapeutic or prophylactic effect in the human subject to whom theactive agent is administered, without undue adverse side effects (suchas toxicity, irritation, or allergic response), commensurate with areasonable benefit/risk ratio when used in the manner of this invention.The specific effective amount will vary with such factors as theparticular condition being treated, the physical condition of thesubject, the nature of concurrent therapy (if any), the specific dosageform, the oral care composition employed, and the desired dosageregimen.

According to one embodiment, the oral composition for use in treatingdentine hypersensitivity is used in a method comprising applying thecomposition to at least one tooth of a patient for an effective amountof time, preferably the composition remains on the at least one toothfor at least 1 min, at least 15 min, at least 30 min, at least 1 hour,at least 2 hours, at least 12 hours or at least 24 hours.

The scope and interest of the present invention will be betterunderstood based on the following figures and examples which areintended to illustrate certain embodiments of the present invention andare non-limitative.

DESCRIPTION OF THE FIGURE

FIG. 1 shows a scanning electron microscope (SEM) micrograph of thesurface-reacted calcium carbonate prepared according to Example 1.

FIG. 2 shows a SEM micrograph of the surface-reacted calcium carbonateprepared according to Example 2.

FIG. 3 shows a SEM micrograph of an untreated bovine tooth neck samplewith open dentinal tubules.

FIG. 4 shows a SEM micrograph of a bovine tooth neck sample that wastreated with the surface-reacted calcium carbonate of Example 1.

FIG. 5 shows a SEM micrograph of a bovine tooth neck sample that wastreated with the surface-reacted calcium carbonate of Example 3.

FIG. 6 shows a SEM micrograph of a bovine tooth neck sample that wastreated with the surface-reacted calcium carbonate of Example 3 and a0.2 M acetic acid solution.

FIG. 7 shows a SEM micrograph of a bovine tooth neck sample that wastreated with a ground calcium carbonate (comparative example).

FIG. 8 shows a SEM micrograph of a bovine tooth neck sample that wastreated with a ground calcium carbonate (comparative example) and a 0.2M acetic acid solution.

EXAMPLES

1. Measurement Methods

In the following, measurement methods implemented in the examples aredescribed.

Particle Size Distribution

The particle size distribution of non surface-reacted calcium carbonateparticles, e.g., ground calcium carbonate, was measured using aSedigraph 5100 from the company Micromeritics, USA. The method and theinstrument are known to the skilled person and are commonly used todetermine grain size of fillers and pigments. The measurement wascarried out in an aqueous solution comprising 0.1 wt.-% Na₄P₂O₇. Thesamples were dispersed using a high speed stirrer and supersonics. Forthe measurement of dispersed samples, no further dispersing agents wereadded.

The volume median grain diameter (d₅₀) of surface-reacted calciumcarbonate was determined using a Malvern Mastersizer 2000 LaserDiffraction System (Malvern Instruments Plc., Great Britain).

Scanning Electron Microscope (SEM) Micrograph

The prepared surface-reacted calcium carbonate and the tooth necksamples were examined by a Sigma VP field emission scanning electronmicroscope (Carl Zeiss AG, Germany) and a variable pressure secondaryelectron detector (VPSE) with a chamber pressure of about 50 Pa.

Specific Surface Area (SSA)

The specific surface area is measured via the BET method according toISO 9277 using nitrogen, following conditioning of the sample by heatingat 250° C. for a period of 30 minutes. Prior to such measurements, thesample is filtered within a Büchner funnel, rinsed with deionised waterand dried overnight at 90 to 100° C. in an oven. Subsequently the drycake is ground thoroughly in a mortar and the resulting powder placed ina moisture balance at 130° C. until a constant weight is reached

Solids Content of an Aqueous Suspension

The suspension solids content (also known as “dry weight”) wasdetermined using a Moisture Analyser MJ33 from the companyMettler-Toledo, Switzerland, with the following settings: dryingtemperature of 160° C., automatic switch off if the mass does not changemore than 1 mg over a period of 30 sec, standard drying of 5 to 20 g ofsuspension.

2. Examples

Example 1 Preparation of Surface-Reacted Calcium Carbonate

In a mixing vessel, 7 liters of an aqueous suspension of ground calciumcarbonate was prepared by adjusting the solids content of a groundcalcium carbonate having a particle size distribution of 90 wt.-% below2 μm, based on the total weight of the ground calcium carbonate,(commercially available from Omya AG, Switzerland) such that a solidscontent of 15 wt.-%, based on the total weight of the aqueoussuspension, is obtained.

232 g phosphoric acid was added in form of an aqueous solutioncontaining 30 wt.-% phosphoric acid to said suspension over a period of30 minutes at a temperature of 70° C. After addition of acid, the slurrywas stirred for additional 5 minutes, before removing from the vessel.

The resulting surface-reacted calcium carbonate had a volume mediangrain diameter (d₅₀) of 2.7 μm, as measured by laser diffraction(Malvern Mastersizer 2000), and a specific surface area of 51.0 m²/g.

A SEM micrograph of the surface-reacted calcium carbonate having aporous platy or lamellar surface structure is shown in FIG. 1.

Example 2 Preparation of Surface-Reacted Calcium Carbonate

In a mixing vessel, 7 liters of an aqueous suspension of ground calciumcarbonate was prepared by adjusting the solids content of a groundcalcium carbonate having a particle size distribution of 90 wt.-% below2 μm, based on the total weight of the ground calcium carbonate,(commercially available from Omya AG, Switzerland) such that a solidscontent of 20 wt.-%, based on the total weight of the aqueoussuspension, is obtained.

320 g phosphoric acid was added in form of an aqueous containing 30wt.-% phosphoric acid to said suspension over a period of 60 minutes ata temperature of 70° C. After addition of acid, the slurry was stirredfor additional 5 minutes, before removing from the vessel.

The resulting surface-reacted calcium carbonate had a volume mediangrain diameter (d₅₀) of 2.4 μm, as measured by laser diffraction(Malvern Mastersizer 2000), and a specific surface area of 48.8 m²/g.

A SEM micrograph of the surface-reacted calcium carbonate having aporous platy or lamellar surface structure is shown in FIG. 2.

Example 3 Preparation of Surface-Reacted Calcium Carbonate

In a mixing vessel, 7 liters of an aqueous suspension of ground calciumcarbonate was prepared by adjusting the solids content of a groundcalcium carbonate having a particle size distribution of 90 wt.-% below2 μm, based on the total weight of the ground calcium carbonate,(commercially available from Omya AG, Switzerland) such that a solidscontent of 20 wt.-%, based on the total weight of the aqueoussuspension, is obtained.

320 g phosphoric acid was added in form of an aqueous solutioncontaining 30 wt.-% phosphoric acid to said suspension over a period of60 minutes at a temperature of 85° C. After addition of acid, the slurrywas stirred for additional 5 minutes, before removing from the vessel.

The resulting surface-reacted calcium carbonate had a volume mediangrain diameter (d₅₀) of 2.1 μm, as measured by laser diffraction(Malvern Mastersizer 2000), and a specific surface area of 20.2 m²/g.

Example 4 Tooth Treatment with Surface-Reacted Calcium Carbonate

The crown section of a bovine molar was separated from the tooth neck bya saw. Subsequently, the following grinding and polishing steps werecarried out on the tooth neck using a Buehler Phoenix 4000 polishingmachine (Buehler GmbH, Germany):

Firstly, the tooth neck was grinded parallel to its longitudinal axisuntil the dentine layer has been reached grinding wheel: Ultraprep 20μm, velocity: 300 rpm, water-cooling). Subsequently, the pre-grindedsurface was polished for 30 s (grinding wheel: Apex, velocity: 300 rpm,water-cooling). Finally, the polished surface was further polished for120 with a polishing cloth (Texmet perforated, velocity: 150 rpm, nowater-cooling).

The polished tooth neck was soaked for 2 min in a 15% EDTA solution andrinsed with tap water.

The prepared tooth neck sample was soaked in the surface-reacted calciumcarbonate suspensions of Example 1, 2 or 3 for 60 s and the toothsurface was brushed for 30 s with a tooth brush. Subsequently, the toothsample was rinsed with tap water.

The tooth neck samples before and after treatment with surface-reactedcalcium carbonate were glued onto a SEM sample holder and examined by aSigma VP field emission scanning electron microscope (Carl Zeiss AG,Germany) and a variable pressure secondary electron detector (VPSE) witha chamber pressure of about 50 Pa.

FIG. 3 shows a scanning electron microscope (SEM) micropgraphs of theuntreated tooth neck sample and FIG. 4 shows a SEM micrograph of a toothneck sample, which was treated with the suspension of surface-reactedcalcium carbonate of Example 1. While the open dentine tubules areclearly visible in the untreated sample shown in FIG. 3, FIG. 4evidences that the dentine tubules have been effectively occluded by thetreatment with the inventive suspension of surface-reacted calciumcarbonate.

Example 5 Resistance to Acid Challenge

A bovine tooth neck sample was prepared by treating a bovine tooth neckwith surface-reacted calcium carbonate of Example 3 according to theprocedure set out in Example 4. The obtained tooth neck sample wassoaked for 10 s in a 0.2 M acetic acid solution. Subsequently, the toothneck sample was rinsed with tap water.

As comparative example, a bovine tooth neck sample was prepared asdescribed in Example 4, but by using a ground calcium carbonate fromAvenza-Carrara, Italy (weight median particle size d₅₀=2.6 μm,commercially available from Omya AG, Switzerland) instead ofsurface-reacted calcium carbonate.

The tooth neck samples before and after treatment with acetic acid wereglued onto a SEM sample holder and examined by a Sigma VP field emissionscanning electron microscope (Carl Zeiss AG, Germany) and a variablepressure secondary electron detector (VPSE) with a chamber pressure ofabout 50 Pa.

FIG. 5 shows a scanning electron microscope (SEM) micrograph of a toothneck sample being treated with the inventive surface-reacted calciumcarbonate of Example 5 before the acid treatment and FIG. 6 shows a SEMmicrograph of such a tooth neck sample after acid treatment. FIG. 7shows a scanning electron microscope (SEM) micrograph of a tooth necksample being treated with the comparative ground calcium carbonatebefore the acid treatment and FIG. 8 shows a SEM micrograph of such atooth neck sample after acid treatment. While the occluded dentinetubules are clearly visible for the inventive sample in FIG. 5, FIG. 7evidences that by using the comparative ground calcium carbonate thedentine tubules are only occluded partially or are not occluded at all.Furthermore, it can be gathered from FIG. 8 that the comparative groundcalcium carbonate has been removed from the tooth surface and thedentine tubules almost completely by the acid treatment. In contrast,the inventive sample shown in FIG. 6 shows that the dentine tubules arestill occluded by the inventive surface reacted calcium carbonate afterthe acid treatment. These results demonstrate that the inventivesurface-reacted calcium carbonate is resistant to an acid challenge froma typical beverage or dish that may be consumed following use of theproduct.

What is claimed is:
 1. An oral care composition comprising: asurface-reacted calcium carbonate that is a reaction product of naturalor synthetic calcium carbonate with carbon dioxide and at least one acidand that is in the form of particles having a volume median graindiameter (d₅₀) of equal to or less than 3 μm and a volume determined topcut particle size (d₉₈) of equal to or less than 6 μm; wherein the atleast one acid is chosen from hydrochloric acid, sulphuric acid,sulphurous acid, phosphoric acid, citric acid, oxalic acid, acetic acidformic acid, and mixtures thereof.
 2. The oral care composition of claim1, wherein contacting of teeth with the oral care composition iseffective to treat dentine hypersensitivity.
 3. The oral carecomposition of claim 1, wherein the oral care composition comprises from1 to 20 wt.-% of the surface-reacted calcium carbonate, based on thetotal weight of the composition.
 4. The oral care composition of claim1, wherein the oral care composition is a toothpaste, a toothpowder, ora mouthwash.
 5. The oral care composition of claim 1, wherein the oralcare comprises at least one active agent associated with thesurface-reacted calcium carbonate.
 6. The oral care composition of claim1, wherein the oral care composition comprises at least one additionaldesensitizing agent chosen from potassium nitrate, glutaraldehyde,silver nitrate, zinc chloride, strontium chloride hexahydrate, sodiumfluoride, stannous fluoride, strontium chloride, strontium acetate,arginine, hydroxyapatite, calcium sodium phosphosilicate, potassiumoxalate, calcium phosphate, calcium carbonate, bioactive glass, andmixtures thereof.
 7. The oral care composition of claim 1, wherein theoral care composition comprises a bioadhesive polymer chosen fromhydroxyethyl methacrylate, PEG/PPG copolymers,polyvinylmethylether/maleic anhydride copolymers, polyvinylpyrrolidone(PVP), cross-linked PVP, shellac, polyethylene oxide, methacrylates,acrylate copolymers, methacrylic copolymers, vinylpyrrolidone/vinylacetate copolymers, polyvinyl caprolactam, polylactides, siliconeresins, silicone adhesives, chitosan, milk proteins (casein),amelogenin, ester gum, and combinations thereof.
 8. The oral carecomposition of claim 1, wherein the surface-reacted calcium carbonatehas a radioactive dentine abrasion (RDA) value of less than
 70. 9. Theoral care composition of claim 1, wherein the surface-reacted calciumcarbonate has a radioactive dentine abrasion (RDA) value of less than50.
 10. The oral care composition of claim 1, wherein the oral carecomposition has a pH between 7.5 and
 10. 11. The oral care compositionof claim 1, wherein the at least one acid is phosphoric acid.
 12. Theoral care composition of claim 1, wherein the surface-reacted calciumcarbonate particles have a volume median grain diameter (d₅₀) of from1.5 to 2.9 μm and/or a volume determined top cut particle size (d₉₈) offrom 3.5 to 5.5 μm.
 13. The oral care composition of claim 1, whereinthe surface-reacted calcium carbonate particles have a volume mediangrain diameter (d₅₀) of from 2.2 to 2.6 μm and/or a volume determinedtop cut particle size (d₉₈) of from 4.5 to 5 μm.
 14. The oral carecomposition of claim 1, wherein the surface-reacted calcium carbonateparticles have a specific surface area of from 5 m²/g to 200 m²/g,measured using nitrogen and the BET method of ISO
 9277. 15. The oralcare composition of claim 1, wherein the surface-reacted calciumcarbonate particles have a specific surface area of from 30 m²/g to 60m²/g, measured using nitrogen and the BET method of ISO
 9277. 16. Theoral care composition of claim 1, wherein the carbon dioxide is formedin situ by the treatment with the at least one acid and/or is suppliedfrom an external source.
 17. The oral care composition of claim 1,wherein the carbon dioxide is formed in situ by the treatment with theat least one acid.
 18. The oral care composition of claim 1, wherein themolar ratio of the at least one acid to the natural or synthetic calciumcarbonate is from 0.5 to
 4. 19. The oral care composition of claim 1,wherein the surface-reacted calcium carbonate is a reaction product ofthe natural calcium carbonate with the carbon dioxide and the at leastone acid in an aqueous suspension.
 20. An oral care compositioncomprising: a surface-reacted calcium carbonate that is a reactionproduct of natural calcium carbonate with carbon dioxide and phosphoricacid, wherein the molar ratio of the phosphoric acid to the naturalcalcium carbonate is from 0.5 to 4, and that is in the form of particleshaving a volume median grain diameter (d₅₀) of from 1.5 to 2.9 μm and avolume determined top cut particle size (d₉₈) of from 3.5 to 5.5 μm;wherein the carbon dioxide is formed in situ by the phosphoric acidtreatment, and contacting of teeth with the oral care composition iseffective to treat dentine hypersensitivity.